PF-06463922

Base Information

• Chemical Name: PF-06463922
• CAS No.: 1454846-35-5
• Molecular Formula: C₂₁H₁₉FN₆O₂
• Molecular Weight: 406.419
• Mol file: 1454846-35-5.mol

Synonyms:

Chemical Property of PF-06463922

Chemical Property:

• Melting Point: 184-187°C
• Boiling Point: 675.0±55.0 °C(Predicted)
• PKA: 6.05±0.40(Predicted)
• Density: 1.42±0.1 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: Chloroform (Slightly), Ethyl Acetate (Slightly)

Purity/Quality:

99.0% MIN ^*data from raw suppliers

Lorlatinib ≥98%(HPLC) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Lorlatinib (PF-06463922) is a new drug under development for the sub-group of advanced non-small cell lung cancerwho are ALK or ROS1 positive and have already undergone gene treatment with drugs thatspecifically targetthis type of cancer.Lorlatinib is currently being evaluated in phase II clinical trials as an oral dose at 100 mg daily. If marketed it will becomean additional targeted treatment for this sub-group of ALKor ROS1 positive patients. Lorlatinib acts by inhibiting the ALK and ROS1 receptor tyrosine kinases, with potent activity against a broad spectrum of ALK resistant mutations. By inhibiting ALK phosphorylation and ROS1 activity, lorlatinib inhibits the downstream signalling, thereby inducing the apoptosis process, which results in the inhibition of tumour cells proliferation. Due to tumor complexity and development of resistance to treatment, disease progression is a challenge in patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). A common site for progression in metastatic NSCLC is the brain. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier.
• Uses: Lorlatinib is a selective tyrosine kinase receptor inhibitor used in the therapy of selected cases of advanced non-small cell lung cancer.Lorlatinib has been used in trials studying the basic science and treatment of Non-small Cell Lung Cancer and anaplastic lymphoma kinase (ALK)-positive Non-Small Cell Lung Cancer (NSCLC) and ROS1-positive NSCLC. Despite initial responses from the use of various ALK inhibitors, however, it is virtually almost guaranteed that all patients with the condition in question will develop tumour progression or resistance to the current therapy in use. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that promotes cell proliferation and blocks apoptosis. PF-06463922 is an ATP-competitive, selective inhibitor of ALK (Ki = < 0.07 nM) and c-Ros oncogene 1 (ROS1, Ki = 0.7 nM). It has strong activity against all known ALK and ROS1 mutants identified in patients, including the EML4-L1196M mutant of ALK (Ki = < 0.02 nM). PF-06463922 is orally available, displaying inhibition of ALK phosphorylation and antitumor efficacy in a xenograft model expressing EML4-L1196M ALK. It demonstrates efficient blood-brain barrier penetration, produces brain tumor regression in mice harboring EML4-ALK tumors, and increases overall survival.[Cayman Chemical] PF- 06463922 is a potent and selective ROS1/ALK inhibitor capable to block crizotinib-resistant ROS1 mutations. Used in the treatment of human cancers.

Technology Process of PF-06463922

There total 61 articles about PF-06463922 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

(10R)-(7-di-tert-butyloxycarbonylamino)-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile → (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (1454846-35-5)

Guidance literature:

With hydrogenchloride; In methanol; water; at 20 ℃; for 2h;

Reference yield: 90.0%

C21H21FN6O3 → lorlatinib (1454846-35-5)

Guidance literature:

With dmap; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In 1,2-dichloro-ethane; at 70 ℃; for 5h;

Reference yield: 89.4%

C21H21FN6O3 → (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (1454846-35-5)

Guidance literature:

With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 50 ℃; for 3h; Temperature; Reagent/catalyst;

upstream raw materials:

((4-bromo-5-cyano-1-methyl-1H-pyrazol-3-yl)methyl)(methyl)carbamic acid tert-butyl ester

1-(5-fluoro-2-iodophenyl)ethan-1-one

(S)-1-(5-fluoro-2-iodophenyl)-ethan-1-ol

2-amino-3-hydroxypyridine

Refernces

• 1、 -. "Preparation method of anti-tumor drug Lorlatinib". Paragraph 0030; 0040-0044; 0054-0057; 0067-0069. . Retrieved 2021/08/21.
• 2、 -. "Preparation method of anticancer drug". Paragraph 0028-0047. . Retrieved 2021/03/13.